Causes of jaundice during hepatic artery infusion chemotherapy

Jaundice develops in many patients with liver metastases from colorectal adenocarcinoma during hepatic arterial infusion chemotherapy (HAIC). The usual cause is thought to be hepatotoxicity from the chemotherapeutic agent or biliary obstruction from progressive neoplastic disease. The authors evaluated the abdominal computed tomography and ultrasound examinations performed on 49 patients who were jaundiced during long-term HAIC. In only one patient was diffuse intrahepatic biliary dilatation caused by an obstructing mass in the porta. Two patients had metastatic hepatic lesions causing focal biliary obstruction. Intrahepatic dilatation without an obstructing mass occurred in 20 patients. Percutaneous or endoscopic cholangiograms were commonly interpreted prospectively as showing extrinsic compression by metastases, but no mass was confirmed on imaging studies. Seven patients had focal intrahepatic ductal dilatation from stricture without an associated mass. The remaining 19 patients had normal-caliber ducts; their jaundice was caused by chemical hepatitis. This series suggests that the most common causes of jaundice in these patients are chemical hepatitis and common bile duct stricture, complications of intraarterial chemotherapy, rather than neoplastic obstruction. Stricture formation may be confused with extrinsic compression on direct cholangiograms.     

Fungal keratitis in far north Queensland,Australia

Background: Aboriginals and Torres Strait Islanders form a significant proportion of the population in far north Queensland and are at increased risk for many eye conditions. This study describes the pattern of fungal keratitis seen at Cairns Base Hospital, far north Queensland, Australia. Methods: A retrospective review of all cases of culture positive fungal keratitis presenting between 1998 and 2008. The records of 17 patients were reviewed for epidemiological, risk factor, microbiological, treatment and outcome data. Results: The study included 16 eyes from 16 patients. Five (31.25%) patients were of Aboriginal and Torres Strait Islander descent. Pre‐disposing factors were ocular trauma (n = 7) and contact lens wear (n = 3). No patients were on topical steroids at presentation. All patients grew filamentous fungi with Fusarium the most common isolate (50%). Aspergillus, Curvularia and Lasiodiplodia theobromae were the next most common accounting for two cases each. Two patients developed corneal perforations, whereas two required penetrating keratoplasty and one required evisceration. Eight patients had a visual acuity of 6/18 or better at presentation and this increased to 13 patients at final follow up. Conclusions: A significant proportion of the patients presenting to Cairns Base Hospital with fungal keratitis are Indigenous. The very high percentage of cases due to filamentous fungi is similar to other tropical regions of the world. The very low rates of Candida infection and steroid use prior to presentation are in contrast to studies from temperate areas such as Melbourne and Philadelphia.     

Androgen dependence of the Dunning R3327G cell line in monolayer culture

For optimal application of new treatment strategies for prostate cancer, the basic biologic effects of androgens on cell kinetics and DNA synthesis require detailed examination. An androgen-responsive prostate cancer cell line in monolayer culture provides a means to study the biochemical mechanisms mediating hormonal stimulation of cell proliferation. We chose to evaluate the proliferative response of the Dunning R3327G tumor cell line (Du-G cells) to 5 alpha-dihydrotestosterone (DHT) in monolayer culture. The DU-G cells grew more rapidly in the presence of increasing concentrations of DHT in the range of 10(-8)-10(-5) M than with vehicle control. At 10(-7) M DHT, 3H-thymidine incorporation increased from 400 +/- 34 counts/min/well to 751 +/- 77 (p less than .01). Effects of DHT were maximal when a plating density of 10,000 cells/well was employed. Androgen effects on cellular growth were reproducible but were limited in magnitude. Rapid metabolism of DHT in culture did not explain this phenomenon. Du-G cells were not completely dependent on androgen, since cells continued to grow in media containing less than 10(-11) M dihydrotestosterone and hydroxyflutamide.     

PSYCHOLOGICAL EFFECTS OF AN EPIDEMIOLOGICAL STUDY OF BENIGN PROSTATIC HYPERTROPHY

SUMMARY The psychological impact of an epidemiological study of benign prostatic hypertrophy (BPH) was assessed in a representative sample of practice list patients. Of the 889 men completing a general health self-report questionnaire previously validated in a screening programme, 75% knew nothing of problems of the prostate, and 84.5% were not at all worried about prostate problems prior to commencement of the study. Receiving the letter of invitation and the procedures neither increased nor reduced anxiety levels for 69% and 70% respectively. In the 227 men referred to hospital for further investigation the procedure increased anxiety in 28%, decreased anxiety in 20%, and had no effect on the remainder. The sample of 137 (16%) men who, prior to interview, were in some way worried about problems of the prostate had significantly more urinary tract symptoms than those who were not at all worried about prostatic problems. Despite being worried about prostatic problems and having significant urinary symptoms, this group was no more likely to have attended a GP for investigation and/or treatment. Results are discussed in relation to the possible psychological effects of general health screening and the reluctance of men to attend for consultation despite awareness and concern regarding urinary symptomatology.     

The inter‐rater reliability between nurse‐assessors clinically assessing infection of chronic wounds using the WUWHS criteria

The aim of this study was to determine the inter‐rater reliability between one expert‐nurse and four clinical‐nurses who were asked to clinically assess infection of chronic wounds by using the World Union of Wound Healing Societies (WUWHS) criteria. A quasi‐experimental design was used to collect the data. In comparison to phase 1 in which ‘open questions’ were asked, in phase 2 a pre‐printed form (checklist) was introduced. In both phases, 55 chronic wounds were clinically assessed. For each WUWHS criterion the inter‐rater reliability of signs and symptoms was expressed by Cohens Kappa (κ). A substantial agreement (κ ≥ 0·6) was considered as adequate. In both phases pocketing (p < 0·02), and erythema (p < 0·004) scored statistically significant results. Phase 2 showed higher inter‐rater agreements compared with phase 1 (three substantial agreements (easily bleeding/friable granulation tissue, delayed healing, increasing exudate), an almost perfect‐ and a perfect agreement for malodour and pain, respectively. According to the results it can be concluded that the clinical assessment of infection of chronic wounds may be better supported by a pre‐printed form than making use of an ‘open questions’ form. To provide this with a higher level of evidence, there is need for more well conducted studies.     

Treatment of compulsive behaviour in eating disorders with intermittent ketamine infusions

We have previously shown that eating disorders are a compulsive behaviour disease, characterized by frequent recall of anorexic thoughts. Evidence suggests that memory is a neocortical neuronal network, excitation of which involves the hippocampus, with recall occurring by re-excitement of the same specific network. Excitement of the hippocampus by glutamate-NMDA receptors, leading to long-term potentiation (LTP), can be blocked by ketamine. Continuous block of LTP prevents new memory formation but does not affect previous memories. Opioid antagonists prevent loss of consciousness with ketamine but do not prevent the block of LTP. We used infusions of 20 mg per hour ketamine for 10 h with 20 mg twice daily nalmefene as opioid antagonist to treat 15 patients with a long history of eating disorder, all of whom were chronic and resistant to several other forms of treatment. Nine (responders) showed prolonged remission when treated with two to nine ketamine infusions at intervals of 5 days to 3 weeks. Clinical response was associated with a significant decrease in Compulsion score: before ketamine, mean +/- SE was 44.0 +/- 2.5; after ketamine, 27.0 +/- 3.5 (t test, p = 0.0016). In six patients (non-responders) the score was: before ketamine, 42.8 +/- 3.7; after ketamine, 44.8 +/- 3.1. There was no significant response to at least five ketamine treatments, perhaps because the compulsive drive was re-established too soon after the infusion, or because the dose of opioid antagonist, nalmefene, was too low.      

美国国家骨髓库无关供者造血干细胞移植20年回顾

自美国国家骨髓库(NMDP)开展第一例无关供者移植以来,至今已有20年.NMDP目前的库容量已逾700万,已为6大洲提供了30 000多份无关供者造血干细胞.这一辉煌成就是美国国家骨髓库600多名工作人员共同努力的结果,同时也得益于广泛的国际合作,包括171个移植中心,73个供者中心,24个脐血库,97个骨髓采集中心,91个血液净化中心,26个HLA分型实验室和26个合作供者登记处.本文回顾了美国国家骨髓库的历史,阐述了20年来移植病人、移植物来源和预处理方案几方面的主要变化趋势.     

Growth hormone therapy for protein catabolism

GH and IGF-I have shown remarkable consistency of effect in a wide range of catabolic conditions. Doses of around 10 IU/m2/day of GH and 80 micrograms/kg/day of IGF-I over short periods of time can improve net protein synthesis and preserve lean body mass. Most studies have reported metabolic endpoints, but favorable clinical effects have included decreased hospital stay and mortality in burns, improved respiratory muscle function in COAD, preserved grip strength post- operatively, and improvements in cardiac and bowel failure. Adverse effects of GH treatment are uncommon and usually related to glycaemic control. GH and IGF-I have differential effects on insulin concentrations--increasing or decreasing concentrations, respectively. The hypoglycaemic effects of IGF-I are dependent on route of administration and are avoided by subcutaneous delivery. Occasional patients have needed to discontinue GH treatment due to hyperglycaemia, although the anabolic action of GH may be partially mediated by increased insulin levels. The co-administration of GH and IGF-I has theoretical advantages by both increasing IGF binding-protein concentrations and balancing glycaemic control. An initial study with combination therapy in calorically-restricted volunteers has shown anabolic effects greater than with either agent alone. This approach requires further study in catabolic patients. There is a need for large, well-designed trials with clinical rather than purely metabolic end-points, and some of these are already underway. Should these studies confirm the early findings, financial considerations will become paramount, although it remains possible that treatment may be self-financing if lengths of hospital admissions are shortened.